rs875525

chr5-14747138-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054027.6(ANKH):c.823-1176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,044 control chromosomes in the GnomAD database, including 11,545 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (11545 hom., cov: 33)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935

Genes affected

ANKH (HGNC:15492): (ANKH inorganic pyrophosphate transport regulator) This gene encodes a multipass transmembrane protein that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. Progressive ankylosis-mediated control of pyrophosphate levels has been suggested as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals. Mutations in this gene have been associated with autosomal dominant craniometaphyseal dysplasia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.823-1176G>A		intron_variant		ENST00000284268.8
ANKH	XM_011514067.2	c.823-1176G>A		intron_variant
ANKH	XM_017009644.3	c.739-1176G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.823-1176G>A		intron_variant		1	NM_054027.6	P1
ANKH	ENST00000503939.5	n.335-1176G>A		intron_variant, non_coding_transcript_variant		3
ANKH	ENST00000515517.1	n.57-1176G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53007 AN: 151926 Hom.: 11509 Cov.: 33

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.327

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.349 AC: 53096 AN: 152044 Hom.: 11545 Cov.: 33 AF XY: 0.342 AC XY: 25372 AN XY: 74292

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0903

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.324

Alfa AF: 0.275 Hom.: 3819

Bravo AF: 0.372

Asia WGS AF: 0.159 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.56
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs875525; hg19: chr5-14747247;